Neurofibromatosis 1
Conditions
Keywords
Neurofibromas, Neurofibromatosis 1, Celecoxib, Celebrex, Peg-Interferon alpha-2b, PEG-Intron, Temozolomide, Temodar, Vincristine Sulfate, Oncovin
Brief summary
Patients with neurofibromatosis type 1 (NF1) commonly develop non-cancerous tumors called plexiform neurofibromas. These tumors can be defined as high-risk when they result in severe pain, physical disability, organ dysfunction and/or become life-threatening. Presently, there is no effective medical therapy to offer patients with high-risk plexiform neurofibromas, and surgery does not provide lasting help. This study will evaluate the effectiveness of two treatment combinations in patients with high-risk plexiform neurofibromas.
Detailed description
The study's design involves treating eligible patients with a combination of celecoxib and pegylated interferon alpha-2b. If the patients have at least a partial response after six months, they may continue on the same treatment for up to two years. If the patient experiences less than a partial response, or has progressive disease after six months of therapy, then vincristine and temozolomide will be added to the celecoxib and interferon alpha-2b backbone. Response to treatment will be assessed after a minimum of six months, presuming the patient has not experienced progressive disease. Total duration of therapy on study is two years for any individual treatment plan.
Interventions
DRUGPeg-Interferon alpha-2b
age and weight dependant
age and weight dependant
DRUGTemozolomide (temodar)
age and weight dependant
DRUGVincristine Sulfate (Oncovin)
age and weight dependant
Sponsors
Corewell Health West
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* High-Risk Plexiform Neurofibromas associated with a diagnosis of NF1 * 2-30 years old (minimum bodyweight of 10 kilograms) * Adequate renal function
Exclusion criteria
* Previously untreated active optic glioma * History of any previous allergy to study medications * History of ischemic vascular disease * Pregnancy / Breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| At Least 50% Shrinkage in Tumor Measurements by Physical Examination | Monthly physical exam first three months and then every three months after, for up to 36 months | — |
| Improvement of Symptoms and Pain | Monthly physical exam first three months and then every three months after, for up to 36 months | Subjects will be evaluated for pain and Quality of Life scores |
| Response by MRI Measurements | evaluated 6, 12 and 24 months compared to baseline | partial response by RICST criteria is defined as \>50% tumor shrinkage |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| No Reported Psychological Toxicity Based Upon Psychological Evaluations | Psychological evaluation at 24 months | Psychological toxicity defined as suicidal ideation |
Countries
United States
Participant flow
Pre-assignment details
Period 1: Baseline to 6 months, Period 2: After 6 month evaluation for addition of vincristine and temozolomide, if accurate and appropriate
Participants by arm
| Arm | Count |
|---|---|
| Open-Label Intervention This is a phase II single arm study with sequential treatments available by response where all participants begin therapy with a combination of celecoxib and interferon alpha-2b (CI, treatment-1). Response to CI therapy will be assessed at six months by clinical and radiographic evaluations. Those patients who have achieved a partial response (improvement in pain, improvement in functioning, or ≥50% reduction in tumor size) or complete response (resolution of pain, and normalization of functioning with a ≥ 90% reduction in tumor size) will continue with the same CI therapy for up-to two years on study.
Peg-Interferon alpha-2b: age and weight dependant
Celecoxib (Celebrex): age and weight dependant
Temozolomide (temodar): age and weight dependant
Vincristine Sulfate (Oncovin): age and weight dependant | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Open-Label Intervention | — |
|---|---|---|
| Age, Categorical <=18 years | 9 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 9 participants | — |
| Sex: Female, Male Female | 4 Participants | — |
| Sex: Female, Male Male | 5 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 1 / 9 |
| serious Total, serious adverse events | 1 / 9 |
Outcome results
Primary
At Least 50% Shrinkage in Tumor Measurements by Physical Examination
Time frame: Monthly physical exam first three months and then every three months after, for up to 36 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-Label Intervention | At Least 50% Shrinkage in Tumor Measurements by Physical Examination | 7 Participants |
Primary
Improvement of Symptoms and Pain
Subjects will be evaluated for pain and Quality of Life scores
Time frame: Monthly physical exam first three months and then every three months after, for up to 36 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-Label Intervention | Improvement of Symptoms and Pain | 9 Participants |
Primary
Response by MRI Measurements
partial response by RICST criteria is defined as \>50% tumor shrinkage
Time frame: evaluated 6, 12 and 24 months compared to baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open-Label Intervention | Response by MRI Measurements | Partial Response at 6 months | 0 participants |
| Open-Label Intervention | Response by MRI Measurements | Complete Response at 6 months | 1 participants |
| Open-Label Intervention | Response by MRI Measurements | Less than Partial Response at 6 months | 8 participants |
| Open-Label Intervention | Response by MRI Measurements | Partial Response at 12 months | 2 participants |
| Open-Label Intervention | Response by MRI Measurements | Complete Response at 12 months | 1 participants |
| Open-Label Intervention | Response by MRI Measurements | Less than Partial Response at 12 months | 6 participants |
| Open-Label Intervention | Response by MRI Measurements | Partial Response at 24 months | 4 participants |
| Open-Label Intervention | Response by MRI Measurements | Less than Partial Response at 24 months | 1 participants |
| Open-Label Intervention | Response by MRI Measurements | no longer participating at 24 months | 3 participants |
| Open-Label Intervention | Response by MRI Measurements | Complete Response at 24 months | 1 participants |
Secondary
No Reported Psychological Toxicity Based Upon Psychological Evaluations
Psychological toxicity defined as suicidal ideation
Time frame: Psychological evaluation at 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-Label Intervention | No Reported Psychological Toxicity Based Upon Psychological Evaluations | 8 Participants |